Cadmium-induced stress: a close look at the relationship between autophagy and apoptosis.

Stress is acknowledged as one of the major factors responsible for autophagy induction, a tightly regulated process that acts as a pro-death or pro-survival mechanism within cells. Cadmium (Cd), a toxic heavy metal, induces apoptosis and autophagy in cells after exposure to low concentrations. This is due to Cd's ability to induce oxidative stress in cells and tissues by overproducing reactive oxygen species. Several proteins have been found to mediate the process of autophagy but aspects of their specific roles and targets remain undefined. Though LC3-II and p62 have traditionally been used as biomarkers that define autophagy, recent findings have revealed some limitations to LC3-II because it can be accumulated in cells in an autophagy-independent manner, whereas p62 remains a good determinant of the process. In addition to LC3-II and p62, recent studies have suggested that a new member of the autophagy protein family, the vacuole membrane protein 1 (VMP1), is essential in driving autophagy and could be an important biomarker for detecting the initiation and progression of autophagy. This review therefore focuses on current trends in autophagy biomarkers, the effect of Cd on the expression of LC3-II, p62, VMP1, and Beclin-1 and their relation and inter-regulatory roles in autophagy and apoptosis, pharmacological importance, and the mechanisms involved.

Distinctive modulation of hepcidin in cancer and its therapeutic relevance.

Hepcidin, a short peptide synthesized primarily by hepatocytes in response to increased body iron and inflammation, is a crucial iron-regulating factor. Hepcidin regulates intestinal iron absorption and releases iron from macrophages into plasma through a negative iron feedback mechanism. The discovery of hepcidin inspired a torrent of research into iron metabolism and related problems, which have radically altered our understanding of human diseases caused by an excess of iron, an iron deficiency, or an iron disparity. It is critical to decipher how tumor cells manage hepcidin expression for their metabolic requirements because iron is necessary for cell survival, particularly for highly active cells like tumor cells. Studies show that tumor and non-tumor cells express and control hepcidin differently. These variations should be explored to produce potential novel cancer treatments. The ability to regulate hepcidin expression to deprive cancer cells of iron may be a new weapon against cancer cells.

Heparin mimetics as potential intervention for COVID-19 and their bio-manufacturing.

The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy. Moreover, after more than 2 years, many populations are still under pressure of infection. Thus, a broader perspective in developing antiviral strategies is still of great importance. Inspired by the observed multiple benefits of heparin in the treatment of thrombosis, the potential of low molecular weight heparin (LMWH) for the treatment of COVID-19 have been explored. Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients, accordingly reducing lethality. Furthermore, several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection. These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates. In this review, we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection, focusing on the perspectives of developing heparin mimetics via chemical synthesis, chemoenzymatic synthesis, and bioengineered production by microbial cell factories. The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.

Role of the calcium-sensing receptor (CaSR) in cancer metastasis to bone: Identifying a potential therapeutic target.

Cancer is a major cause of morbidity and mortality worldwide due to its ability to evade immune surveillance and metastasize from its origin to a secondary point of contact. Though several treatment techniques have been developed to suppress or manage cancer spread, a strategy for total control over the disease continues to evade researchers. In considering ways to control or prevent cancer from metastasizing to the bone, we analyze the impact of the calcium-sensing receptor (CaSR), whose primary role is to maintain calcium (Ca2+) homeostasis in cellular and systemic physiological processes. CaSR is a pleiotropic receptor capable of enhancing the proliferation of some cancers such as breast, lung, prostate and kidney cancers at its primary site(s) and stimulating bone metastasis, while exerting a suppressive effect in others such as colon cancer. The activity of CaSR not only increases cancer cell proliferation, migration and suppression of apoptosis in the organs indicated, but also increases the secretion of parathyroid hormone-related protein (PTHrP) and epiregulin, which induce osteolytic activity and osteoblastic suppression. In addition, released cytokines and Ca2+ from bone resorption are critical factors that further promote cancer proliferation. In this review, we seek to highlight previous viewpoints on CaSR, discuss its role in a new context, and consider its potential clinical application in cancer treatment.

Nephrotoxicity Profile of Cadmium Revealed by Proteomics in Mouse Kidney.

Cadmium (Cd) is a highly toxic metal and kidney is its main target. However, the molecular effects and associated potential impacts of Cd-accumulated kidney have not been well investigated. In this study, mouse was used as a model to investigate the Cd-induced proteomic profile change in kidney, and a total of 34 differentially expressed proteins were detected by two-dimensional gel electrophoresis (2-DE) and further identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Through Gene Ontology analysis and KEGG pathway annotation, it showed that Cd-regulated kidney metabolism and promoted renal damage and cell migration. By validation of Western blotting and RT-qPCR, metastasis-related proteins LIM and SH3 domain protein 1 (LASP1) and phosphoenolpyruvate carboxykinase/cytosolic [GTP] (PEPCK1) were confirmed to be upregulated; Acyl-CoA synthetase medium-chain family member 3 (ACSM3) was downregulated. Furthermore, carcinoma development-related proteins initiation factor 4A (eIF4A) and pyridoxine-5'-phosphate oxidase (PNPO) were upregulated, and pyridoxal kinase (PK) was downregulated. The downregulation of Na(+)/H(+) exchange regulatory cofactor (NHERF3) might promote renal damage which associated with decrease of transferrin (TRF) in kidney. Taken together, our results revealed proteomic profile of Cd-induced nephrotoxicity and provided data for further insights into the mechanisms of Cd toxicity.